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Abstract
Purpose This study conducted in Dena County is a population-based cohort study as part of the Prospective Epidemiological Research Studies in Iran (PERSIAN). The specific objectives of this study were to estimate the prevalence of region-specific modifiable risk factors and their associations with the incidence of major non-communicable diseases (NCDs).
Participants This PERSIAN Dena Cohort Study (PDCS) was conducted on 1561 men and 2069 women aged 35–70 years from October 2016 in Dena County, Kohgiluyeh and Boyer-Ahmad Province, Southwest Iran. The overall participation rate was 82.7%.
Findings to date Out of 3630 participants, the mean age was 50.16 years, 2069 (56.9%) were women and 2092 (57.6%) were rural residents. Females exhibited higher prevalence rates of diabetes, hypertension, fatty liver, psychiatric disorders, thyroiditis, kidney stones, gallstones, rheumatic disease, chronic lung disease, depression and osteoporosis compared with males (p<0.05). Furthermore, the urban population showed elevated rates of diabetes, thyroiditis, kidney stones and epilepsy, whereas psychiatric disorders and lupus were more prevalent in rural areas (p<0.05). According to laboratory findings, 418 (13.0%), 1536 (48.1%) and 626 (19.3%) of the participants had fasting blood sugar >126 mg/dL, low-density lipoprotein >100 mg/dL and haematuria, respectively; most of them were female and urban people (p<0.05).
Future plans PDCS will be planned to re-evaluate NCD-related incidence, all-cause and cause-specific mortality every 5 years, along with annual follow-up for 15 years. Some examples of additional planned studies are evaluation of genetic, environmental risk, spirometry and ECG tests.
- EPIDEMIOLOGY
- NUTRITION & DIETETICS
- PUBLIC HEALTH
Data availability statement
Data are available upon reasonable request. This research is still under progress and the general information is available at www.yums.ac.ir/cohort and http://persiancohort.com/. Due to ethical and legal concerns, the supporting data could not be publicly available. However, following assessment and approval of their request by the steering committee for the DENA cohort, interested researchers may obtain the necessary data. Researchers who are interested in accessing the data should contact the corresponding author, M-RJ (mr.jowshan@gmail.com). For possible collaborations, interested peers should contact the corresponding author and submit their proposal to the Yasuj University of Medical Sciences (YUMS).
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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STRENGTHS AND LIMITATIONS OF THIS STUDY
The research’s most significant benefit lies in its prospective method.
A large sample size facilitated accurate comparisons of illnesses and risk factors.
The study could register persons from both urban and rural locations.
The study’s extensive use of clinical, demographic, genetic and laboratory variables made it applicable to future studies assessing the relationship between various diseases and associated factors.
Assessing the role of risk factors in developing rare consequences can be challenging.
Introduction
In recent years, evidence-based decision-making has been widely used to improve policymaking and planning strategies in public health systems.1 Adopting this approach is highly recommended for the prevention, care, management and control of non-communicable diseases (NCDs).2 3 In Iran, like other developing countries experiencing an epidemiological transition stage, the prevalence of communicable diseases has decreased significantly due to socioeconomic improvements, and NCDs have become the main cause of death that necessitates comprehensive prevention and control measures.4–7
NCDs cause 41 million deaths annually worldwide (72.3% of all deaths in 2016).8 WHO reports that NCDs in 2020 were responsible for 82% of deaths in Iran in 2020 (43% cardiovascular diseases, 16% cancers and 23% other NCDs).9 The rise of NCDs poses a new challenge to Iranian healthcare.10 NCDs caused 15.5 million disability-adjusted life-years (DALYs) in 2019, representing a 44.2% increase from 1990. Ischaemic heart disease remained the largest cause of age-standardised DALY rates, followed by stroke, diabetes, lower back pain and depressive disorders. Diabetes showed the greatest 30-year change, an approximately twofold rise. Furthermore, NCD-related deaths in Iran increased by 88.0% since 1990, reaching 326 508 in 2019. Premature deaths (30–70 years old) caused by the four major NCDs accounted for 52.7% of all-age mortality in 1990, rising to 37.1% (100 893 deaths) in 2019. Cardiovascular diseases were the leading cause of early death in 2019, accounting for around 54.6%.11
The reports have indicated the severity of the upcoming epidemic of NCDs and their metabolic risk factors in Iran. To reduce the heavy financial burden of NCDs, it is necessary to implement effective prevention and treatment plans. A health economic analysis has shown that disease prevention is cost-effective for improving public health. Effective prevention strategies for NCDs require accurate information about their causes and risk factors. Large population-based prospective cohort studies are ideal for investigating the effects of lifestyle factors, genetic predisposition, and socioeconomic, occupational, and psychological factors on the incidence of NCDs. Accordingly, there should be a plan for early diagnosis and prevention of NCDs (especially for the elderly), reducing health costs and increasing the quality of life.12–14 Finally, even though NCDs have a substantial influence on both the economy and the health of Iran, public health institutions and the general population in Iran still need to give sufficient attention to these issues.
Conducting a prospective cohort study can significantly contribute to the evidence needed to identify disease aetiology and risk factors. Since many NCDs take decades to develop, exposure to risk factors is necessary to development of these diseases. Therefore, only longitudinal monitoring and accurate recording of exposures can help identify risk factors and possible causes.12 15 Since the initiation of the Framingham Heart Study in 1948 (the first modern population-based cohort study), this type of research has gained wide acceptance in developed countries. However, in developing countries, cohort studies are scarce. The findings from cohort studies conducted in developed countries can be applied to developing countries like Iran.16 17
In view of genetic diversity, social and environmental exposures, lifestyle and other factors can influence the development of NCDs to different degrees in each geographical region. Also, the existence of diverse ethnicities in Iran emphasises the importance of conducting longitudinal studies in different regions of Iran. Therefore, this study aimed to assess the incidence of major NCDs and the role of risk factors in the development of various chronic diseases. As part of the Prospective Epidemiological Research Studies in Iran (PERSIAN), this population-based cohort study focused on establishing a biobank for basic scientific research and creating a platform for population-based clinical trials to explore low-cost interventions.
Cohort description
Overview
This PERSIAN cohort study conducted in Dena County is a subset of a more extensive PERSIAN cohort study (http://persiancohort.com). The PERSIAN cohort study was designed and conducted in 2014, comprising different geographical, ethnical and climatic groups in 18 provinces of Iran, to investigate NCDs in Iranian adults aged 35–70 years.18 This PERSIAN Dena Cohort Study (PDCS) is 1 of the 18 cohort studies of Iran, which commenced in Southwest Iran in February 2016 with a total follow-up span of 15 years. The study will be repeated every 5 years to track changes and trends.
Target region and target population
Dena is a county in the north of Kohgiluyeh and Boyer-Ahmad Province in Southwest Iran, covering 1821 km². Its name is derived from the Dena Mountain range, the highest fold of the Zagros Mountains. Dena is located on the slopes of the Dena Mountains. The city has a mountainous climate and is snow-covered for most autumn and winter. According to the latest census in 2016, it has more than 42 539 people, including 21 467 males (50.5%) and 21 072 females (49.5%). Of the total population, 23.8% are urban and 76.2% are rural settlers. Dena County has two cities (ie, Pataveh and Sisakht) and four counties. The capital of the county is Sisakht. People aged 35–70 years should participate in the cohort study as a target group. The inclusion criteria were men and women aged 35–70 years old, with a duration of residence in the study area of more than 1 year, sufficient physical and mental ability to participate in the evaluation programme, and signing a written consent form. Exclusion criteria were defined as the inability to attend the clinic for a physical examination, mental retardation and unwillingness to participate in the study. The PERSIAN cohort studies focus on diverse Iranian ethnicities, including Fars (Persians), Turks/Azari, Kurds, Lurs, Baloch, Arabs, etc, with unique cultural practices and lifestyles, making their exposure diverse. Since most of the population in Dena County is of Lur ethnicity, it was chosen to represent Lurs.19 Figure 1 shows the location of this study.
The map of Iran. The location of Kohgiluyeh and Boyer-Ahmad Province (source: Management and Planning Organization of Kohgiluyeh and Boyer-Ahmad Province, Iran National Cartographic Center).
Enrolment phase
Preparation stage
All necessary equipment was provided based on the PERSIAN cohort protocol and Dena cohort proposal, including buildings (registration room, medical examination room, nutritional consultant room, anthropometric room, follow-up room, management room, waiting room and kitchen/rest room), laboratory unit, storage room (refrigerated/freezer storage, non-refrigerated storage), archival unit for documents and records, biological biobank environment with four refrigerators, temperature monitoring system, uninterruptible power supply and standard questionnaires.18–20 Subsequently, consumable and non-consumable tools, physical space, and human resources were examined and evaluated using a checklist. Qualified internal and external observers were then selected.
PDCS resources
A professional team participated in the study daily, including doctors, interviewers, nurses, sample technologists, a manager, a supervisor and a driver. A master’s or bachelor’s degree was required for interviewers trained to deliver and complete the questionnaires. The Iran Ministry of Health, Treatment and Medical Education requires interviewers to have a valid certificate. The interviewers received face-to-face training, mostly in workshops, in three main phases, as well as monthly and extraoccupational training. The primary management team consisted of a geneticist, epidemiologist, statistician, psychologist and cardiologist. The technical and scientific advisory team included a nutritionist, gastroenterologist, internist, pulmonologist, nephrologist, medical informatics specialist, medical geneticist, oncologist, radiologist, orthopaedist, molecular medicine specialist, surgeon disease specialist, health specialist, pharmacist, neurologist, nurse and ophthalmologist. A laboratory and biobank, totalling around 170 m2, were also established, along with a 13-person interview station, management team, and other units for recording exposures and collecting group data. PDCS staff members consisted of a receptionist, a field facilitator, a medical interviewer, two general interviewers, a person in charge of the anthropometric device, a nutritionist, a sampling expert, a technician responsible for the central biobank, two people in charge of the quality control of the cohort centre, a person responsible for the follow-up of the group and the head of the cohort centre (a health education specialist), a general practitioner, two experimenters and interviewers who were present at the cohort centre at certain times practically every day (figure 2).
The organisational chart of the PERSIAN Dena Cohort Study. PERSIAN, Prospective Epidemiological Research Studies in Iran; PI, principal investigator.
Participant recruitment
At baseline in this study, multiple coordination meetings were held between specialists and subordinate authorities to select the sites and sample in this cohort. Subsequently, the interviewers and trained health workers (Behvarz workers) conducted door-to-door visits in both rural and urban areas to inform individuals about the study and its objectives, and provided them with a pamphlet for further details. In the Iranian health network model, Behvarz workers are typically selected from the local population to interface between the people and the health system. They receive training in maternal and child health, communicable diseases and environmental health to continue educating the community.21 After identifying households and their order of entry into the study, the protocol for participants to enter the study was established. Health houses prepared a list of qualified people before they visited households. The list was finalised following the visits and invitations.
This list included name, last name, age, gender, proportion of family members and contact number. The interviewers were fluent in the native language of the region, and the participants were invited to an interview. The time of the interview at the cohort centre was announced to the participants. They were asked not to cut or colour their hair for 2–4 weeks, not to cut or colour their nails for 7–10 days, and maintain clean hair for at least 10–12 hours before the interview. Participants were also asked to bring their ID cards and medication to the interview session. The admissions officer of the cohort centre contacted participants 1 week before the interview date (based on the invitation list) and provide them with the time and details of participation. The host contacted everyone again a day before the event to provide a reminder. The invitation call was repeated up to three times when no participants were present.
Registration phase
The aims of the study were explained in detail to participants, and written informed consent was obtained from all participants. Each participant received an 11-digit code (PERSIAN cohort identifier) after registration, indicating their place of residence/habitation and familial status. Weight (kg), height (cm), wrist circumference (WrC; cm), waist circumferences (WC; cm) and hip circumference (HC; cm) were measured. Blood samples were collected in tubes containing clot activator or anticoagulation. Blood samples were collected in the morning after an overnight fast. The samples were stored in codified tubes and containers. A total of 25 mL of blood was collected using one 7 mL clot tube and three 6 mL EDTA tubes. Approximately 500 hairs (1–3 cm in length) and 1 mm of nail clippings from all fingers were collected. Participants were then welcomed and given complimentary baskets containing food and beverages. Data on general health, personal life, work experience, lifestyle, physical activity, nutrition, medical examination, frequency, prevalence and history of NCDs were collected using electronic questionnaires. In addition, data on exposure to and risk factors for NCDs were documented. Online supplemental files 1 and 2 and online supplemental table 1 present the tools used in this cohort study. Also, all variables are available in online supplemental file 3: data dictionary for baseline variables.
Supplemental material
Supplemental material
Supplemental material
Supplemental material
Instruments of data collection, exposures and specimens
Questionnaire
Standard electronic questionnaires18 with confirmed validity and reliability were used in this PDCS (online supplemental file 1 (questionnaire) and online supplemental file 2 (questionnaire in the original language)). Online supplemental table 1 presents the tools used in this cohort study.
Physical examination
Using a standard mercury sphygmomanometer (Richter, MTM Munich, Germany), systolic and diastolic blood pressures were measured twice (ie, after a 5-minute rest in a sitting position and 15 min later based on the protocols on the right arm). A minimum of 5 min passed between each of the two 60-second measurements of the heart rate. In a health centre, trained healthcare providers measured anthropometric data, including weight, height, WrC, WC and HC.
The height was measured using a stadiometer (Seca 755 1021994, Germany): the participants stood against a wall with their heels and buttocks in contact. Weight was measured using a standing scale (Seca 755 1021994, Germany), calibrated with a 5 kg before the weight measurement. In addition, removing excess clothing and shoes was recommended to ensure accurate measurements. WrC, WC and HC were measured to the nearest 0.1 cm using a flexible metric measuring tape (Seca 755 1021994, Germany). HC and WC were measured in a standing position, with HC measured at the level of the maximum posterior extension of the buttocks in a horizontal plane. WC was determined in duplicate midway between the lowest rib crest and the upper edge of the iliac crest. WrC was measured in a standing position with the anterior-up wrist using a tension-gated tape measure stretched across Lister’s tubercle of the distal radius and across the distal ulna on both arms. Lying flat on the skin, the tape measure was not used too tightly or loosely.
Specimens
Some of the blood samples were used for biochemical and haematological assays, including fasting blood sugar (FBS), serum cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, triglycerides, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, creatinine, complete blood cell count and erythrocyte sedimentation rate. According to standard laboratory protocols and using Pars Azmoon kits (Pars Azmoon Co, Iran), all measurements were performed using a biochemistry autoanalyser (BT1500, 47173738, Italy) and haematology cell counter (Sysmex, XP (B0463), Japan).
The laboratory data were stored in an electronic database. The remaining blood specimens were stored at –80°C for future analysis. Additionally, the collected urine samples were kept at –20°C for macroscopic and microscopic analysis. Online supplemental table 2 presents the division and separation of blood samples, urine samples, hairs and nails for each individual in the biobank.
Supplemental material
There were 12-digit barcodes on every tube that could be easily read by a barcode scanner. The samples were put in a specific order in the box codified for every participant. Nail and hair samples were wrapped in foil and then packed in individual zip bags with dehumidifiers. Then, the bags were labelled with participant codes and kept at room temperature.
Follow-up and outcome determination
Once a year, all participants receive phone calls to follow up on issues such as the occurrence of accidents, death, cancer, diabetes, and cardiovascular, gastrointestinal, pulmonary, and neurological diseases. The follow-up team, including a physician/nurse, interviewers and a laboratory technician, will visit participants at home and conduct an in-person interview if the phone calls are not returned after six attempts on 3 separate days over 3 weeks. A health worker assists with this procedure for the rural population. Moreover, participants were asked to inform the follow-up team in case of new major disease presentations. The follow-up team visits the relevant medical centres where participants were hospitalised, or diagnostic/therapeutic procedures were performed. All clinical, pathology and hospital records will be collected. The participants will be personally visited if there was a challenge.
An outcome review team, including the follow-up team and three internists, will determine the final diagnosis or the cause of any death of participants by consulting their medical histories, hospital records and cancer registries, as well as other registries, such as the hospital information system (SEPAS electronic health certificate system; http://tebyangroup.com/samaneh-sepas/) and SIB network (sib.iums.ac.ir). The SIB network belongs to a prospective population-based cohort study in which the demographic information and administrative health data for >88% of Iranians (about 72 million people) are registered.22 The final diagnosis will be defined based on the International Classification of Diseases, 10th edition. In case of inconsistencies, a third blind specialist evaluated all documents, and his/her decision will be considered the final diagnosis. A verbal autopsy will be carried out to ascertain the cause of death if death was recorded, but no valid death certificate was present.
The findings were retrieved from SEPAS and SIB using national codes. We have already completed the third annual follow-up and are now at the end of the fourth annual follow-up with a participation rate of 95%. We designed to resurvey the whole enrolment phase, including 2000 participants every 5 years; we have now followed up 700 people.
Quality control of the study
The study’s quality control team comprised two national and university/executive-level individuals. Additionally, faculty members from the epidemiology and laboratory sciences departments made up the quality control team at the university level. A two-person team of epidemiology and laboratory science experts performed field quality control at all phases of data collection, including interviews, invitations, censuses, sampling, performing tests and directly documenting their results. Moreover, checklists were used to monitor job steps and study time. The data were then compared with the results of the e-questionnaires.
Data management and statistical analysis
Data management
Data were entered and validated once each group of interviews was completed. The supervisor at the centre has assessed the relevance of the data. Missing or incorrect data were retrieved after assessing the process and talking with a related interviewer. The data entry software evaluated the surveys for completeness and consistency while they were being entered.
Statistical analysis
All data were descriptively analysed using the SPSS V.26 software. A qualified statistician assessed the accuracy of the final data. The numerical data were reported as mean and SD. A χ2 test was employed to analyse the connection between nominal and grouped variables. A p value of <0.05 was considered statistically significant.
Patient and public involvement
Not applicable.
Findings to date
A total of 3630 people were recruited through 5110 phone invitations, resulting in a participation rate of 82.7%. The most common reasons for not participating were being too busy and lack of interest. All processes of this cohort study are shown in online supplemental figure 1. The demographic and socioeconomic characteristics of the studied population are presented in table 1. All demographic characteristics were significantly different between males and females in the total population and between urban and rural regions (p<0.001).
Supplemental material
Demographic and socioeconomic characteristics of participants by gender and habit in PERSIAN Dena Cohort Study
The anthropometric and clinical characteristics of participants are illustrated in table 2. Most of the females (n=882; 42.7%) were obese. Notably, the rate of abdominal obesity was higher in females than in males (92.7% vs 84.9%). Similarly, the rates of good physical activity and enough sleep were higher in females than in males (p<0.001). Additionally, the rate of inadequate sleep was higher in urban people than in rural people (50.2% vs 33.8%).
The anthropometric and clinical characteristics of participants by gender and habit in PERSIAN Dena Cohort Study
The prevalence rates of diabetes, hypertension, fatty liver, psychiatric disorders, thyroiditis, kidney stones, gallstones, rheumatic disease, chronic lung disease, depression and osteoporosis were higher in females than in males (p<0.05). Meanwhile, the prevalence rates of diabetes, thyroiditis, kidney stones and epilepsy were higher in urban people than in rural people. However, the prevalence rates of psychiatric disorders and lupus were higher in rural people than in urban people (p<0.05). In addition, the laboratory findings of participants are demonstrated in table 3. According to the laboratory findings, 418 (13.0%), 1536 (48.1%) and 626 (19.3%) of the participants had FBS >126 mg/dL, LDL >100 mg/dL and and haematuria, respectively; most of them were female and urban people (p<0.05).
Laboratory findings by gender and habit in PERSIAN Dena Cohort Study
Data availability statement
Data are available upon reasonable request. This research is still under progress and the general information is available at www.yums.ac.ir/cohort and http://persiancohort.com/. Due to ethical and legal concerns, the supporting data could not be publicly available. However, following assessment and approval of their request by the steering committee for the DENA cohort, interested researchers may obtain the necessary data. Researchers who are interested in accessing the data should contact the corresponding author, M-RJ (mr.jowshan@gmail.com). For possible collaborations, interested peers should contact the corresponding author and submit their proposal to the Yasuj University of Medical Sciences (YUMS).
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by the Ethical Review Board of Kohgiluyeh and Boyer-Ahmad University of Medical Sciences (code: YUMS (IR.YUMS.REC.1401.040)). The aims of the study were completely explained to the participants, and also informed consent forms were obtained from all participants. In addition, the results of the study are available to the participants. The participants were free to leave the study at any time. A codified confidential database was used to store data.
Acknowledgments
We thank all the participants, staff members and health volunteers who attended in this cohort. We are also grateful to Hossein Poustchi and Sareh Eghtesad, for their assistance and support and for valuable expertise for the study.
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
X @MrJowshan
Contributors JH and RG collaborated in the management and design of the study. RG and FJ supervised the entire study process. FJ, M-RJ, M-AZ, MKS, AH and MH had a major contribution to writing the manuscript. ZK and FR designed and revised the figure. RG and SAS conducted the data analysis. M-RJ, FJ and JH were in charge of the critical review and editing of the manuscript. M-RJ is guarantor of the study. All authors read and approved the final manuscript.
Funding The financial and non-financial support for this study was provided by the Ministry of Health, Treatment and Medical Education of Iran and Yasuj University of Medical Sciences (YUMS).
Map disclaimer The depiction of boundaries on this map does not imply the expression of any opinion whatsoever on the part of BMJ (or any member of its group) concerning the legal status of any country, territory, jurisdiction or area or of its authorities. This map is provided without any warranty of any kind, either express or implied.
Competing interests None declared.
Patient and public involvement Patients or the general public were not involved in the planning or design, recruitment or conduction of the study.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.